HIV-associated dementia (HAD) involves destruction of neurons and synapses. Brain inflammatory cells, including brain microglia and invading blood monocytes, participate in this CNS-damaging pathway by release of neurotoxins. We have identified drugs that are highly protective against inflammatory cell mediated neuron injury. Some of these agents are also able to reduce brain inflammation in the HIV/AIDS volunteers. This fast track SBIR proposal seeks to develop a new drug formulation with neuroprotective effects against CMS injury in HIV/AIDS. In Phase I, we will optimize pharmaceutical properties of a new formulation in vitro, establish an effective dosing schedule for neuroprotection in man, and determine pharmacokinetic profiles in human volunteers. The goal of Phase 2 will be to advance the new drug formulation into a clinical trial using HIV/AIDS volunteers. A 12-week double-blinded, placebo controlled study will determine the ability of the new drug formulation to alter a biomarker of brain inflammation and to improve cognition during the treatment period.